TABLE 1

Decision matrix

BZDOKTMXOXSB
UV-visible spectral analysis
MEC (M−1⋅cm−1)2317a10,833a4350a2850a6817a11,700a
ROS assay
1O2 (ΔA440 nm⋅103)b219aN.D.318a67a,c147aN.D.
O2 (ΔA560 nm⋅103)dN.D.N.D.94aN.D.cN.D.N.D.
3T3 NRU PT
PIF49.5a1.068.9aN.A.1.01.0
PK analysis after dermal coadministratione
Tmax (h)46248624
Cmax (μg/g tissue)6.1 ± 0.66.0 ± 1.08.7 ± 0.9a7.8 ± 0.57.8 ± 1.27.8 ± 0.5
AUC0–24 (h⋅μg/g tissue)64.5 ± 2.853.4 ± 3.1160.0 ± 7.387.6 ± 4.098.6 ± 5.1133.5 ± 7.4
MRT (h)8.4 ± 0.37.2 ± 0.3>14.2a8.4 ± 0.29.3 ± 0.2>14.9a
  • AUC0–24, area under the concentration versus time curve from 0 to 24 hours. N.A., not applicable due to solubility issue; N.D., not detected.

  • a High levels of each crucial factor: MEC values over 1000 M−1⋅cm−1 in the UV-visible spectral analysis; ROS data over criteria in the ROS assay (1O2 [ΔA440 nm⋅103]: 25; and O2 [ΔA560 nm⋅103]: 20); PIF values over criteria in the 3T3 NRU PT (PIF: 5); and higher values of PK parameters (Cmax and MRT) in the PK analysis.

  • b Decrease in A440 nm⋅103.

  • d Increase in A560 nm⋅103.

  • c ROS data from irradiated MX (100 μM).

  • e Cmax and MRT values were used as crucial factors for in vivo phototoxic prediction. Each value represents mean ± S.E. for five rats.